Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role ofLimosilactobacillus reuteriin releasing IL-22 (LR-IL-22) as an effective radiation mitigator, and we have now assessed its effect in an ovarian cancer mouse model. We hypothesized that an LR-IL-22 gavage would enable intestinal radioprotection by modifying the tumor microenvironment and, subsequently, improving overall survival in female C57BL/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer. Herein, we report that the LR-IL-22 gavage not only improved overall survival in mice when combined with a PD-L1 inhibitor by inducing differential gene expression in irradiated stem cells but also induced PD-L1 protein expression in ovarian cancer cells and mobilized CD8+ T cells in whole abdomen irradiated mice. The addition of LR-IL-22 to a combined treatment modality with fractionated whole abdomen radiation (WAI) and systemic chemotherapy and immunotherapy regimens can facilitate a safe and effective protocol to reduce tumor burden, increase survival, and improve the quality of life of a locally advanced ovarian cancer patient.
尽管癌症治疗近期取得了进展，卵巢癌仍是全球致死率最高的妇科恶性肿瘤，因此建立新型治疗策略至关重要且具有重大意义。辅助性放射治疗在历史上曾被评估，但其应用因肠道毒性而受限。我们近期证实了罗伊氏乳杆菌释放IL-22（LR-IL-22）作为有效辐射缓解剂的作用，并在卵巢癌小鼠模型中评估了其效果。我们假设LR-IL-22灌胃可通过改变肿瘤微环境实现肠道辐射防护，进而提高腹腔广泛转移同源2F8cis卵巢癌的雌性C57BL/6MUC-1小鼠的总体生存率。本研究表明，LR-IL-22灌胃与PD-L1抑制剂联用不仅通过诱导受辐射干细胞的差异基因表达提高小鼠总体生存率，还能诱导卵巢癌细胞PD-L1蛋白表达，并在全腹腔照射小鼠中动员CD8+ T细胞。将LR-IL-22加入包含分次全腹照射、全身化疗及免疫疗法的联合治疗方案，可形成安全有效的治疗策略，从而减轻肿瘤负荷、提高生存率并改善局部晚期卵巢癌患者的生活质量。
肿瘤(癌症)患者之家